Development of a Lyophilized Formulation of Pegaspargase and Comparability Versus Liquid Pegaspargase

Adv Ther. 2019 Aug;36(8):2106-2121. doi: 10.1007/s12325-019-00988-5. Epub 2019 May 28.

Abstract

Introduction: Pegaspargase, a pegylated asparaginase, is a core component in the treatment of acute lymphoblastic leukemia. Pegaspargase in liquid form has a limited shelf life of 8 months due to depegylation, leading to changes in purity and potency over time. Lyophilization is an approach that can improve the stability of biological drug conjugates.

Methods: Here we describe the development of a lyophilized formulation of pegaspargase and present results of a series of tests demonstrating that the lyophilized form has comparable physicochemical properties to the liquid form.

Results: Stability tests of critical quality attributes, including purity, potency, aggregates and total free polyethylene glycol, demonstrate that lyophilized pegaspargase remains stable for at least 3 years, with optimum stability achieved with storage under refrigerated conditions (2-8 °C).

Conclusions: Lyophilization improved the stability of pegaspargase without altering other physicochemical properties, permitting a prolonged shelf life of at least 2 years when stored at 2-8 °C. This may enable greater storage flexibility and allow for better management of pegaspargase.

Funding: Study Sponsor: Baxalta (now part of Takeda). Publication Sponsor: Servier Affaires Médicales.

Keywords: Cancer chemotherapy; Enzymes; Formulation; Lyophilization; Pediatric; Pegylation; Stability; Stabilization.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Asparaginase / therapeutic use*
  • Drug Compounding*
  • Drug Stability*
  • Freeze Drying*
  • Humans
  • Polyethylene Glycols / therapeutic use*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*

Substances

  • Antineoplastic Agents
  • Polyethylene Glycols
  • pegaspargase
  • Asparaginase

Associated data

  • figshare/10.6084/m9.figshare.8101064